Drive Mechanism for a Drug Delivery Device

ABSTRACT

The present invention relates to a drive mechanism of a drug delivery device for setting and dispensing of a dose of a medicament, the mechanism comprising: a housing ( 20 ), a piston rod ( 120 ) to operably engage with a piston ( 14 ) of a cartridge ( 12 ) to displace the piston ( 14 ) in a distal direction ( 1 ), a rotatable member ( 80 ) arranged on an axially extending axis of rotation ( 4 ) in the housing ( 20 ), said rotatable member ( 80 ) being rotatable in a dose incrementing direction ( 5 ) against the action of a spring element ( 78 ) and being operably engageable with the piston rod ( 120 ) during dose dispensing, a clutch member ( 150 ) comprising at least one radially displaceable clutch element ( 153 ) to engage with a rim ( 82 ) of the rotatable member ( 80 ) with variably adjustable strength.

The present invention relates to a drive mechanism for a drug deliverydevice and to a respective drug delivery device. In particular, theinvention relates to an injection device such like a pen-type injectorinter alia comprising a single and/or a last-dose limiting mechanism andfurther comprising a comparatively large dose indicating display.

BACKGROUND AND PRIOR ART

Drug delivery devices for setting and dispensing a single or multipledoses of a liquid medicament are as such well-known in the art.Generally, such devices have substantially a similar purpose as that ofan ordinary syringe.

Drug delivery devices, in particular pen-type injectors have to meet anumber of user-specific requirements. For instance, with patient'ssuffering chronic diseases, such like diabetes, the patient may bephysically infirm and may also have impaired vision. Suitable drugdelivery devices especially intended for home medication therefore needto be robust in construction and should be easy to use. Furthermore,manipulation and general handling of the device and its componentsshould be intelligible and easy understandable. Moreover, a dose settingas well as a dose dispensing procedure must be easy to operate and hasto be unambiguous.

Typically, such devices comprise a housing or a particular cartridgeholder, which is adapted to receive a cartridge at least partiallyfilled with the medicament to be dispensed. The device further comprisesa drive mechanism, usually having a displaceable piston rod which isadapted to operably engage with a piston of the cartridge. By means ofthe drive mechanism and its piston rod, the piston of the cartridge isdisplaceable in a distal or dispensing direction and may therefore expela predefined amount of the medicament via a piercing assembly, which isto be releasably coupled with a distal end section of the housing of thedrug delivery device.

The medicament to be dispensed by the drug delivery device is providedand contained in a multi-dose cartridge. Such cartridges typicallycomprise a vitreous barrel sealed in distal direction by means of apierceable seal and being further sealed in proximal direction by thepiston. With reusable drug delivery devices an empty cartridge isreplaceable by a new one. In contrast to that, drug delivery devices ofdisposable type are to be entirely discarded when the medicament in thecartridge has been completely dispensed or used-up.

With such multi-dose drug delivery devices at least a last dose limitingmechanism is required to inhibit setting of a dose exceeding the amountof medicament left in the cartridge. This is to avoid a potentiallydangerous situation for the user believing that a set dose is entirelyinjected. There already exist some drug delivery devices withend-of-content mechanisms or last dose mechanisms.

Drug delivery devices such like pen type injectors also provide a doseindicating mechanism which is operable to display the size of a set doseto a user. Typically, the housing of such drug delivery devicescomprises a dose indicating window in which a number representing thesize of the dose shows up.

Especially with elderly patients or users suffering impaired vision,reading of such dose indicating numbers is sometimes difficult. Withdevices adapted for injection of e.g. insulin, typical dose sizes mayvary between 0 and 120 I.U. (International Units) of insulin. Due to therather compact design and limited geometrical dimensions of typical drugdelivery devices the size of such dose indicating numbers is fairlysmall. For visually impaired persons correct reading of comparativelytiny numbers may therefore be rather difficult. However, since such drugdelivery devices are intended for self-medication treatment, it is ofimportance, that the user is able to correctly determine the size ofdose actually set.

OBJECTS OF THE INVENTION

It is therefore an object of the present invention to avoiddisadvantages of known drug delivery devices and to provide a drivemechanism of a drug delivery device allowing for an intuitive operation,both for setting and for dispensing of a dose. It is another object toprovide a dose indicating mechanism which is easy and unequivocal toread even for persons suffering impaired vision.

In another object, the invention serves to provide a drive mechanism ofa drug delivery device for setting and dispensing of a dose of amedicament and further featuring a single and/or a last dose limitingmechanism.

It is a further aim to provide a drug delivery device comprising such adrive mechanism and comprising a cartridge sealed with a piston andbeing operably engaged with a piston rod of such drive mechanism. Thedrug delivery device should be rather easy and intuitive to handle.

SUMMARY OF THE INVENTION

In a first aspect a drive mechanism for a drug delivery device isprovided for dispensing of a dose of a medicament. The drive mechanismcomprises a housing extending in an axial direction. The housing may beof substantially tubular or cylindrical shape that allows gripping andoperating of the drive mechanism, hence of the entire drug deliverydevice by one hand of a user. The housing may also be of rectangular orcubic shape which may smoothly fit into a palm of a user's hand.

The drive mechanism further comprises a piston rod to operably engagewith a piston of a cartridge containing the medicament to be dispensedby the drive mechanism. The cartridge comprises a piston, which, bymeans of a displacement in axial distal direction, serves to expel anamount of the medicament from the cartridge corresponding to the axialdisplacement of the piston. The piston typically seals the cartridge inaxial proximal direction. The piston rod serves to displace the pistonof the cartridge in an axial distal direction. The piston rod istherefore operable to apply distally directed thrust or pressure to thepiston of the cartridge for displacing the same in distal direction fora predetermined distance that corresponds to a respective amount of themedicament to be dispensed.

The drive mechanism further comprises a rotatable member arranged on anaxially extending axis of rotation in the housing. The rotatable memberis rotatable in a dose setting direction against the action of a springelement and is further operably engageable with the piston rod duringdose dispensing, in which the rotatable member typically rotates in adose decrementing direction. The rotatable member may comprise anelongated rod or a sleeve extending in axial direction and beingrotatably supported in the housing with regard to the axially extendingaxis of rotation.

The housing of the drive mechanism or the entire drug delivery devicemay be elongated as well in axial direction. For instance, the drugdelivery device may comprise a pen-injector which is intended to beclasped and taken by a user's hand. In typical embodiments the axis ofrotation and the elongation of the housing both point in the samedirection. The axis of rotation may coincide with the longitudinaldirection of the housing, of the cartridge and hence of the piston rod.Coincidence of the axis of rotation with a longitudinal direction of anyof the components, housing, piston rod or cartridge means that the axisof rotation extends substantially parallel to the elongation of housing,piston rod or cartridge.

However, in other embodiments the rotatable member, hence the axialdirection may extend at a certain angle with respect to the elongationof the housing, the piston rod or the cartridge. It is generallyconceivable, that the rotatable member is arranged at a predefined anglewith respect to the elongation of the housing. The rotatable member canbe for instance implemented in a dose setting member provided andlocated in a sidewall portion of the housing, thereby extendingsubstantially perpendicular to the longitudinal direction of thehousing.

In other embodiments the rotatable member may comprise a component ofthe drive mechanism operable to transfer angular momentum between aspring-biased drive element, such like a spring element and the pistonrod for driving the piston rod in a dose dispensing direction, hence indistal direction with respect to the axial elongation of the housing.

The rotatable member may either directly or indirectly engage with thepiston rod during dose dispensing for exerting a driving force to thepiston rod by way of which the piston rod can be advanced in distal,hence in dose dispensing direction.

Furthermore, the drive mechanism comprises a clutch member comprising atleast one radially displaceable clutch element to engage with an outerrim of the rotatable member with variably adjustable strength. Theclutch member is particularly operable to hold and to stop e.g. aspring-induced rotational displacement of the rotatable member.Moreover, the clutch element may not only engage and release with therotatable member but is further adapted to variably adjust a mechanicalinteraction, typically a holding or frictional force between astationary clutch member and the rotatable member.

The clutch member is particularly adapted to apply a holding force ofvariable size to the outer rim of the rotatable member. Preferably, theclutch member is adapted to exert a gradually or continuously variableforce or friction effect onto the outer rim of the rotatable member. Inthis way, the mechanical resistance the rotatable member experiences bythe clutch member can be gradually and/or continuously varied.

In a dose setting mode, the clutch member is preferably operable toprovide a holding force so that the rotatable member is secured againstan inadvertent returning rotation in a dose decrementing direction,which points in opposite direction compared to the dose setting or doseincrementing direction. In this way, the clutch member serves as aratchet member allowing the rotatable member to be rotated in doseincrementing direction during dose setting and to inhibit self-actingcounter-directed rotation of the rotatable member in a dose decrementingdirection.

Typically, the rotatable member is rotatable against the action of thespring element during dose setting. During dose dispensing, the energystored in the biased spring element is releasable in a controlled way inorder to drive the rotatable member in the opposite sense, hence in thedose decrementing direction.

By providing a clutch member which is operable to apply a holding forceto the rotatable member with variably adjustable strength or magnitude,the friction or mechanical resistance provided by the clutch member canbe individually modified.

In this sense, the clutch member does not only serve to either hold orto release the rotatable member against or with the action of the springelement but provides an effective means to variably release therotatable member by means of a variable holding force. When in dosedispensing mode, the clutch member at least continuously and graduallyreleases the rotatable member. Then, a respective rotation may smoothlydevelop under the action of the spring element.

Here, the spring element is supposed to provide a substantially constantdriving force to the rotatable member effective to rotate the rotatablemember in the dose decrementing direction. As soon as the holding forceof the clutch member equals the driving force of the spring element therotatable member will start to rotate in dose decrementing direction.With a further gradual decrease of the clutch member's holding force,the angular velocity of the rotatable member may gradually increaseaccordingly. This way, the clutch member serves to individually modifythe angular velocity of the rotatable member for a dose dispensingprocedure.

Preferably, the clutch member and in particular the engagement of itsclutch element with the outer rim of the rotatable member iscontrollable by a user of the drug delivery device. In this way, theuser himself may individually and intuitively choose a suitable angularvelocity of the rotatable member and may therefore determine thevelocity of the advancing motion of the piston rod during a dosedispensing procedure.

By means of the clutch member variably adjustable with the rotatablemember of the drive mechanism the injection velocity of the drivemechanism can be arbitrarily and gradually modified according to auser's request.

In another embodiment, the clutch element is pivotally supported inradial direction. Here, the radial direction is related to the axis ofrotation of the rotatable member which defines the axis of rotation. Byhaving a clutch element pivotally supported in radial direction, bypivoting said clutch element radially inwardly or radially outwardly adecreasing and/or increasing mechanical interaction between the clutchelement and the outer rim of the rotatable member can be attained.

Generally, the at least one clutch element of the clutch member may bepositioned radially outside the outer rim of the rotatable member. Then,a radially inwardly directed displacement of the clutch element mayincrease a retarding force effect on the rotatable member.

In an alternative embodiment, the at least one clutch element isarranged radially inside e.g. a hollow-shaped rim of the rotatablemember. Then, by biasing or stressing the clutch element radiallyoutwardly against the rim of the clutch member may have a comparableretarding force effect on the rotation of the rotatable member.

Irrespective of the mutual arrangement and the concrete number of clutchelements, the at least one clutch element may be resiliently deformablein radial direction according to a further embodiment. Here, the clutchelement may be integrally formed with the clutch member. Preferably,clutch member and clutch element comprise a resiliently deformablethermoplastic material, providing a well-defined elastic modulus.

The mechanical interaction between the at least one clutch element andthe rim of the clutch member may be similar to the embodiment with aradially pivotable clutch element. However, a resiliently deformableclutch element is beneficial in terms of mutually assembling the clutchmember and the at least one clutch element. In particular, when the atleast one clutch element is integrally formed with the clutch member,the number of parts of the drive mechanism can be substantially reduced.

In a further embodiment, the clutch element comprises an arc-shape andat least partially extends along the outer circumference of the outerrim of the rotatable member. Here, it is of particular benefit, when theclutch element comprises a free end section to engage with the rim ofthe rotatable member in a variably adjustable way. The overall length ofthe arc-shaped clutch element and the material of the clutch elementand/or of the integrally formed clutch member is made of, may preciselydetermine the resilient properties and the mechanical response of theclutch element in regard of externally applied manipulating orregulating forces.

In a further embodiment, the clutch element comprises a radiallyinwardly extending lug at a free end portion thereof to engage with theouter rim of the rotatable member. The lug or nose portion at the freeend portion of the clutch element provides a well-defined mutualengagement between the outer circumference of the rim and the clutchelement. Preferably, the outer rim comprises a specific structure tooperably engage with the radially inwardly extending lug of the clutchelement. For instance the outer rim may comprise a number of teeth ormay be designed as a toothed rim. A toothed structure of the rim may bebeneficial to implement a discrete ratchet functionality between theclutch member and the rotatable member, especially during dose setting.

In a further embodiment, the clutch element and the outer rim of therotatable member are frictionally engageable. Here, the clutch element,in particular it's radially inwardly extending lug and the outer rim ofthe rotatable member comprise a friction enhancing surface structure.Typically, mutually and directly engaging portions of the clutch elementand the outer rim may comprise a well-defined roughness allowing tomodify the frictional engagement there between. Moreover, by means of aparticular combination of mating materials, a specific friction effectbetween the clutch element and the rim of the rotatable member can beattained.

In a further but alternative embodiment the clutch element and therotatable member are positively engageable. Here, the clutch member andthe clutch element may substantially implement a ratchet member and aratchet element, respectively. An outer gearing of the rim may thencorrespond and engage with a radially inwardly extending geared lug ofthe clutch element.

Preferably and according to another aspect the clutch element and theouter rim of the rotatable member are frictionally as well as positivelyengageable. It is for instance conceivable, that application of amaximum holding force by the clutch member to the toothed rim ispredominately governed by a purely frictional engagement. As soon as theholding force is gradually decreased, mutually corresponding slopes oredges of e.g. toothed structures of the outer rim and the clutch elementmay start to frictionally slide with respect to each other.

When matching pair of inter-engaging teeth of the clutch element and ofthe outer rim, respectively, slip apart so that a neighbouring tooth ofe.g. the toothed outer rim consecutively engages with the radiallyinwardly extending tooth or lug of the clutch element another, andinitially friction-based sliding of the next tooth of the outer rim ofthe rotatable member relative to the lug of the clutch element may takeplace in a similar way.

The velocity of a mutual slipping of inter-engaging slopes or flanks ofa gear rim with the radially inwardly extending lug is predominantlygoverned and controlled by the force the clutch element is radiallyinwardly engaged with the rim of the rotatable member. By graduallyreducing the radially inwardly directed holding force onto the rotatablemember, the velocity of the rotation of the rotatable member relative tothe clutch element may increase accordingly.

According to another embodiment, the drive mechanism also comprises aregulating member at least radially enclosing the clutch element andcomprising a biasing member to radially engage with the clutch element.The biasing member of the regulating member is displaceable relative tothe clutch element in such a way, that a radially inwardly directedforce exertable by means of the clutch element onto the outer rim of therotatable member can be gradually and arbitrarily adjusted.

Here, it is conceivable, that the biasing member itself is radiallydisplaceable in order to modify the radial position, in particular theradial position of the free end of the clutch element relative to theouter rim of the rotatable member. Preferably, the biasing member isassembled and arranged radially outside the clutch element so as toexert a radially inwardly directed force effect onto the clutch memberon demand.

The regulating member may comprise a rotatable rod featuring aneccentrically arranged or eccentrically-shaped biasing member. Byrotating the regulating member accordingly, a variable radially inwardlydirected force effect can be applied to the clutch element on demand.

According to a further embodiment, the regulating member is rotatablerelative to the clutch element. In this way, the biasing member can bedisplaced along the outer circumference of the arc-shaped clutchelement. Hence, a position or point of mutual and direct engagement ofthe biasing member with the clutch element can be arbitrarily modifiedalong the circumference of its arc-shape.

In this way, a radially inwardly acting support for the arc-shapedclutch element can be variably positioned along the outer circumferenceof the arc-shaped clutch element, hence along its tangential direction.In this way, the effective length or circumference of the arc-shapedclutch element can be modified accordingly thereby effectively modifyingthe resilient behaviour of the resiliently deformable clutch element.

In a further embodiment, the regulating member is rotatable relative tothe clutch element. Here, the regulating member may comprise asleeve-like shape or sleeve-like geometry. The regulating member, hencethe sleeve portion thereof may axially abut with the clutch member.Preferably, the clutch member comprises a cupped-shape with a sidewallportion. In a typical embodiment, the rotatable member, hence its outerrim is enclosed in the cupped receptacle of the clutch member. Moreover,the sleeve of the regulating member may flush and may axially abut withthe tubular sidewall portion of the clutch member.

According to a further embodiment, the regulating member comprises anaxially extending sleeve portion having at least one inclined groove orslit engaged with at least one axially displaceable pin of a dosedispensing member. The dose dispensing member may comprise a dosedispensing button slidably supported at a proximal end of the housing.For dispensing of a dose, the dose dispensing member may be depressed indistal direction, e.g. by means of a user's thumb. Since the dosedispensing member is axially slidably disposed relative to the housing,the pin of the dose dispensing member is only axially displaceable in anon-rotative way relative to the housing.

Since the groove or slit, effectively serving as a coulisse, extends ata predetermined lead or in an inclined direction relative to the axialdirection, hence in an inclined way relative to the axis of rotation ofthe rotatable member, a purely axially-directed and non-rotative motionof the at least one pin, e.g. invoked by a correspondingdistally-directed displacement of the dose dispensing member, leads to arespective rotation of the regulating member relative to the clutchmember.

In this way, the biasing member of the regulating member may slide alongthe arc-shaped clutch element to vary the radially inwardly-directedtension thereof. Depending on the overall geometry and slope of the atleast one groove or slit, the rotational behaviour in response of adistally-directed depression of the dose dispensing member or dosedispensing button can be arbitrarily modified.

In effect, depression of the dose dispensing button in distal directionmay gradually transfer into a respective angle of rotation of theregulating member and may then be gradually transferred into arespective gradual and radially directed adjustment of the clutchelement. In this way, the amount of distally-directed displacement ofthe dose dispensing button may directly transfer to a varying velocityof a dose dispensing rotation of the rotatable member. Generally, alarge displacement path of the dose dispensing member transfers to acomparatively large dispensing velocity.

A rather small displacement path of the dose dispensing member maycorrelate with a comparatively slow and long-lasting dose dispensingprocedure. In this way, the user himself may individually andintuitively decide, on the fly, if the set dose is to be dispensedrather rapidly or in a comparatively slow and long-lasting way.

In a further embodiment, the dose dispensing member is slidably axiallydisplaceable relative to the regulating member against the action of aspring element. Preferably, the spring element may be arranged axiallybetween an inside portion of a proximal end face of the dose dispensingmember and a proximal end face of the clutch member. A release of thedose dispensing member may then immediately return the dose dispensingmember into its proximal stop position, thereby rotating the regulatingmember in the opposite sense of rotation. As a consequence, the biasingmember will return along the outer circumference of the arc-shapedclutch element to increase the holding force to be exerted by the sameon the outer rim of the rotatable member.

Furthermore and according to another embodiment, the mutual engagementof dose dispensing member, regulating member, clutch member androtatable member is such that an angular velocity of a spring elementinduced rotation of the rotatable member in a dose dispensing directionis adjustable by the axial displacement of the dose dispensing memberrelative to the regulating member.

As already described above, axial displacement of the dose dispensingmember relative to the regulating member serves to rotate theaxially-fixed regulating member in a direction in which the biasingmember thereof serves to either decrease or to increase a holding forceto be exerted onto the rim of the rotatable member by the clutch elementof the clutch member.

In a further embodiment, the position of the at least one groove or slitof the regulating member substantially axially flushes with a radiallyinwardly extending notch provided at an outer circumference of theclutch member when the dose dispensing member is located in a proximalstop position. In this embodiment, that the at least one radiallyinwardly extending pin of the dose dispensing member may even leave thegroove or slit of the regulating member in axial proximal direction andto enter the radially inwardly extending notch of the clutch member.

In this way, an initial distally-directed displacement of the dosedispensing member at the beginning of a dose dispensing procedure maynot yet have an effect on the orientation of the regulating member.During such an initial period of axial displacement, the radiallyinwardly extending pin would be just axially guided through the axiallyextending notch of the clutch member. In this way, the dose dispensingmember or dose button could be distally displaced for a certain distancebefore a gradual decoupling of the clutch member is initiated ortriggered.

The notch of the clutch member may be further beneficial for a finalassembly of the drive mechanism. In this way, the radially inwardlyextending pins of the dose dispensing member can be axially and distallyguided along and past the clutch member to axially enter groove or slitof the regulating member.

During this initial phase of distally-directed displacement of the dosedispensing member, another clutch mechanism of the drive mechanism, byway of which mechanical energy can be stored in the drive mechanism mayoperably engage with the piston rod before the rotatable member isreleased for transmitting angular momentum thereto.

In this way, the additional clutch mechanism, e.g. between a drivesleeve and a drive wheel of the drive mechanism and the mechanicalengagement of the clutch member with the rotatable member can besequentially activated or deactivated for inducing a dose dispensingaction. This way it can be ensured, that the mechanical energy to bestored by the spring element does not dissipate in an uncontrolled way.Before the spring element-driven dose decrementing rotation of therotatable member is released and set free, it is guaranteed, that therotatable member is operably engaged with the piston rod.

In an alternative embodiment it is also conceivable, that the radiallyinwardly extending pin of the dose dispensing member is permanentlyengaged with the regulating member. Here, a similar two-stepfunctionality could be attained by modifying the shape and slope of theregulating member's groove or slit accordingly.

In a further embodiment, the rotatable member comprises a drive spindlerotatably engaged with a rotatable dose setting member for rotating thedose setting member in a dose decrementing direction during dosedispensing. For dose setting, the drive spindle is rotatable in theopposite direction, hence in dose incrementing direction through awell-defined interaction with the dose setting member. The dose settingmember may be manually operable by a user and may serve to rotate thedrive spindle in a dose incrementing way against the action of thespring element.

Here, the spring element may comprise a helical spring or a compressionspring. A helical spring is particularly adapted to directly induce adose decrementing rotation onto the drive spindle whereas a compressionspring to be compressed in axial direction may engage with an axiallydisplaceable drive member threadedly engaged with the drive spindle toform a spindle gear.

Additionally or alternatively, the rotatable member may be implementedas a drive sleeve to be rotated in a dose incrementing direction againstthe action of e.g. a helical spring. With a variety of conceivableimplementations of the rotatable member, e.g. in form of a drive spindleor in form of a drive sleeve it is preferred, that the rotatable memberis permanently engaged with a dose indicating arrangement operably toinstantly show the size of the actual dose to a user.

During dose setting, the dose indicating arrangement indicates the sizeof the dose actually set and may typically illustrate a series ofincreasing dose size indicating numbers when the dose is increasedduring dose setting. However, during dose dispensing, the previously setand displayed numbers will decrement accordingly until a zero doseconfiguration at the end of a dose dispensing procedure is reached.

Even though the embodiment as illustrated in the appended Figures onlyshows a single implementation of the rotatable member with a clutchmember, the described and claimed principle of having an adjustableclutch member engaging with a rotatable member can be arbitrarilyimplemented in a large variety of drive mechanisms for drug deliverydevices, such like pen-like injectors.

According to another aspect, the invention also relates to a drugdelivery device for dispensing of a dose of a medicament. The drugdelivery device comprises a drive mechanism as described above and acartridge at least partially filled with the medicament to be dispensedby the drug delivery device. The cartridge is arranged in the housing ofthe drive mechanism or in a cartridge holder of the drug delivery devicewhich is fixed to the housing either releasably or non-releasably, e.g.in case of a reusable or in case of a disposable drug delivery device,respectively. Consequently, the drug delivery device comprises acartridge holder to receive and to accommodate a cartridge filled withthe medicament.

Apart from that, the drug delivery device and the drive mechanism maycomprise further functional components, such like a dose injectionmember, by way of which a user may trigger and control the drug deliverydevice and its drive mechanism for dispensing of a dose of themedicament.

In the present context, the distal direction points in the direction ofthe dispensing and of the device, where, preferably a needle assembly isprovided having a double-tipped injection needle that is to be insertedinto biological tissue or into the skin of a patient for delivery of themedicament.

The proximal end or proximal direction denotes the end of the device ora component thereof, which is furthest away from the dispensing end.Typically, an actuating member is located at the proximal end of thedrug delivery device, which is directly operable by a user to be rotatedfor setting of a dose and which is operable to be depressed in distaldirection for dispensing of a dose.

The term “drug” or “medicament”, as used herein, means a pharmaceuticalformulation containing at least one pharmaceutically active compound,

wherein in one embodiment the pharmaceutically active compound has amolecular weight up to 1500 Da and/or is a peptide, a proteine, apolysaccharide, a vaccine, a DNA, a RNA, an enzyme, an antibody or afragment thereof, a hormone or an oligonucleotide, or a mixture of theabove-mentioned pharmaceutically active compound,

wherein in a further embodiment the pharmaceutically active compound isuseful for the treatment and/or prophylaxis of diabetes mellitus orcomplications associated with diabetes mellitus such as diabeticretinopathy, thromboembolism disorders such as deep vein or pulmonarythromboembolism, acute coronary syndrome (ACS), angina, myocardialinfarction, cancer, macular degeneration, inflammation, hay fever,atherosclerosis and/or rheumatoid arthritis,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one peptide for the treatment and/or prophylaxis ofdiabetes mellitus or complications associated with diabetes mellitussuch as diabetic retinopathy,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one human insulin or a human insulin analogue orderivative, glucagon-like peptide (GLP-1) or an analogue or derivativethereof, or exendin-3 or exendin-4 or an analogue or derivative ofexendin-3 or exendin-4.

Insulin analogues are for example Gly(A21), Arg(B31), Arg(B32) humaninsulin; Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29) humaninsulin; Asp(B28) human insulin; human insulin, wherein proline inposition B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein inposition B29 Lys may be replaced by Pro; Ala(B26) human insulin;Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) humaninsulin.

Insulin derivates are for example B29-N-myristoyl-des(B30) humaninsulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl humaninsulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin;B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30human insulin; B29-N—(N-palmitoyl-Y-glutamyl)-des(B30) human insulin;B29-N—(N-lithocholyl-Y-glutamyl)-des(B30) human insulin;B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin andB29-N-(ω-carboxyheptadecanoyl) human insulin.

Exendin-4 for example means Exendin-4(1-39), a peptide of the sequenceH-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala -Pro-Pro-Pro-Ser-NH2.

Exendin-4 derivatives are for example selected from the following listof compounds:

H-(Lys)4-des Pro36, des Pro37 Exendin-4(1-39)-NH2,

H-(Lys)5-des Pro36, des Pro37 Exendin-4(1-39)-NH2,

des Pro36 Exendin-4(1-39),

des Pro36 [Asp28] Exendin-4(1-39),

des Pro36 [IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39); or

des Pro36 [Asp28] Exendin-4(1-39),

des Pro36 [IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-939),

des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39),

wherein the group -Lys6-NH2 may be bound to the C-terminus of theExendin-4 derivative;

or an Exendin-4 derivative of the sequence

des Pro36 Exendin-4(1-39)-Lys6-NH2 (AVE0010),

H-(Lys)6-des Pro36 [Asp28] Exendin-4(1-39)-Lys6-NH2,

des Asp28 Pro36, Pro37, Pro38Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro38 [Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,

H-des Asp28 Pro36, Pro37, Pro38 [Trp(O2)25] Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38[Trp(O2)25, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36 [Met(O)14, Asp28] Exendin-4(1-39)-Lys6-NH2,

des Met(O)14 Asp28 Pro36, Pro37, Pro38 Exendin-4(1-39)-NH2,

H-(Lys)6-desPro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5 des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Lys6-des Pro36 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,

H-des Asp28 Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25]Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(S1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2;

or a pharmaceutically acceptable salt or solvate of any one of theafore-mentioned Exendin-4 derivative.

Hormones are for example hypophysis hormones or hypothalamus hormones orregulatory active peptides and their antagonists as listed in RoteListe, ed. 2008, Chapter 50, such as Gonadotropine (Follitropin,Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin),Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin,Buserelin, Nafarelin, Goserelin.

A polysaccharide is for example a glucosaminoglycane, a hyaluronic acid,a heparin, a low molecular weight heparin or an ultra low molecularweight heparin or a derivative thereof, or a sulphated, e.g. apoly-sulphated form of the above-mentioned polysaccharides, and/or apharmaceutically acceptable salt thereof. An example of apharmaceutically acceptable salt of a poly-sulphated low molecularweight heparin is enoxaparin sodium.

Antibodies are globular plasma proteins (˜150kDa) that are also known asimmunoglobulins which share a basic structure. As they have sugar chainsadded to amino acid residues, they are glycoproteins. The basicfunctional unit of each antibody is an immunoglobulin (Ig) monomer(containing only one Ig unit); secreted antibodies can also be dimericwith two Ig units as with IgA, tetrameric with four Ig units liketeleost fish IgM, or pentameric with five Ig units, like mammalian IgM.

The Ig monomer is a “Y”-shaped molecule that consists of fourpolypeptide chains; two identical heavy chains and two identical lightchains connected by disulfide bonds between cysteine residues. Eachheavy chain is about 440 amino acids long; each light chain is about 220amino acids long. Heavy and light chains each contain intrachaindisulfide bonds which stabilize their folding. Each chain is composed ofstructural domains called Ig domains. These domains contain about 70-110amino acids and are classified into different categories (for example,variable or V, and constant or C) according to their size and function.They have a characteristic immunoglobulin fold in which two β sheetscreate a “sandwich” shape, held together by interactions betweenconserved cysteines and other charged amino acids.

There are five types of mammalian Ig heavy chain denoted by α, σ, ε, γ,and μ. The type of heavy chain present defines the isotype of antibody;these chains are found in IgA, IgD, IgE, IgG, and IgM antibodies,respectively.

Distinct heavy chains differ in size and composition; α and γ containapproximately 450 amino acids and σ approximately 500 amino acids, whileμ and ε have approximately 550 amino acids. Each heavy chain has tworegions, the constant region (C_(H)) and the variable region (V_(H)). Inone species, the constant region is essentially identical in allantibodies of the same isotype, but differs in antibodies of differentisotypes. Heavy chains γ, α and σ have a constant region composed ofthree tandem Ig domains, and a hinge region for added flexibility; heavychains μ and σ have a constant region composed of four immunoglobulindomains. The variable region of the heavy chain differs in antibodiesproduced by different B cells, but is the same for all antibodiesproduced by a single B cell or B cell clone. The variable region of eachheavy chain is approximately 110 amino acids long and is composed of asingle Ig domain.

In mammals, there are two types of immunoglobulin light chain denoted byλ and κ. A light chain has two successive domains: one constant domain(CL) and one variable domain (VL). The approximate length of a lightchain is 211 to 217 amino acids. Each antibody contains two light chainsthat are always identical; only one type of light chain, κ or λ, ispresent per antibody in mammals.

Although the general structure of all antibodies is very similar, theunique property of a given antibody is determined by the variable (V)regions, as detailed above. More specifically, variable loops, threeeach the light (VL) and three on the heavy (VH) chain, are responsiblefor binding to the antigen, i.e. for its antigen specificity. Theseloops are referred to as the Complementarity Determining Regions (CDRs).Because CDRs from both VH and VL domains contribute to theantigen-binding site, it is the combination of the heavy and the lightchains, and not either alone, that determines the final antigenspecificity.

An “antibody fragment” contains at least one antigen binding fragment asdefined above, and exhibits essentially the same function andspecificity as the complete antibody of which the fragment is derivedfrom. Limited proteolytic digestion with papain cleaves the Ig prototypeinto three fragments. Two identical amino terminal fragments, eachcontaining one entire L chain and about half an H chain, are the antigenbinding fragments (Fab). The third fragment, similar in size butcontaining the carboxyl terminal half of both heavy chains with theirinterchain disulfide bond, is the crystalizable fragment (Fc). The Fccontains carbohydrates, complement-binding, and FcR-binding sites.Limited pepsin digestion yields a single F(ab′)2 fragment containingboth Fab pieces and the hinge region, including the H—H interchaindisulfide bond. F(ab′)2 is divalent for antigen binding. The disulfidebond of F(ab′)2 may be cleaved in order to obtain Fab′. Moreover, thevariable regions of the heavy and light chains can be fused together toform a single chain variable fragment (scFv).

Pharmaceutically acceptable salts are for example acid addition saltsand basic salts. Acid addition salts are e.g. HCI or HBr salts. Basicsalts are e.g. salts having a cation selected from alkali or alkaline,e.g. Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), whereinR1 to R4 independently of each other mean: hydrogen, an optionallysubstituted C1-C6-alkyl group, an optionally substituted C2-C6-alkenylgroup, an optionally substituted C6-C10-aryl group, or an optionallysubstituted C6-C10-heteroaryl group. Further examples ofpharmaceutically acceptable salts are described in “Remington'sPharmaceutical Sciences” 17. ed. Alfonso R. Gennaro (Ed.), MarkPublishing Company, Easton, Pa., U.S.A., 1985 and in Encyclopedia ofPharmaceutical Technology.

Pharmaceutically acceptable solvates are for example hydrates.

It will be further apparent to those skilled in the pertinent art thatvarious modifications and variations can be made to the presentinvention without departing from the spirit and scope of the invention.Further, it is to be noted, that any reference signs used in theappended claims are not to be construed as limiting the scope of thepresent invention.

BRIEF DESCRIPTION OF THE DRAWINGS

In the following, various embodiments of the invention will be describedby making reference to the drawings, in which:

FIG. 1 schematically illustrates a front view of the drug deliverydevice,

FIG. 2 shows a side view of the drug delivery device,

FIG. 3 shows another side view as seen from the opposite side comparedto FIG. 2,

FIG. 4 shows a transverse cross-section through the drug delivery deviceaccording to A-A according to FIG. 2,

FIG. 5 is an exploded view of the components of the drive mechanism,

FIG. 6 shows a perspective isolated view of a dose indicatingarrangement as seen from the front,

FIG. 7 shows the dose indicating arrangement according to FIG. 6 fromthe back side,

FIG. 8 shows an enlarged view of the dose indicating and dose settingarrangement according to FIG. 7,

FIG. 9 shows a transverse cross-section B-B according to FIG. 2,

FIG. 10 is an isolated view of the interleaved first and second doseindicating wheels as seen from the front,

FIG. 11 shows the wheels according to FIG. 10 from the back side,

FIG. 12 shows a perspective and partially cut view of the doseindicating wheels assembled in the housing,

FIG. 13 shows a partially cut and perspective view of the drive spindlearranged in the housing,

FIG. 14 is a partially cut- and enlarged view of the drive sleeve,

FIG. 15 is a perspective view of the mutual engagement of drive sleeve,drive spindle and drive member,

FIG. 16 shows a perspective view of a drive wheel engaged with thepiston rod,

FIG. 17 shows an isolated side view of the drive mechanism without thehousing,

FIG. 18 schematically shows the mutual interaction of the drive spindlewith the drive sleeve,

FIG. 19 shows a configuration of the drive mechanism with the drivemember in its proximal stop position,

FIG. 20 schematically illustrates the assembly of the drive mechanisminside a lower housing portion,

FIG. 21 shows a cross-section along B-B together with the dosedispensing button,

FIG. 22 shows an enlarged perspective view of the mutual engagement ofthe dose setting button with a regulating member,

FIG. 23 shows a cross-section B-B according to FIG. 2 with theregulating member in a release configuration,

FIG. 24 shows a perspective view according to FIG. 22 with the dosedispensing button fully depressed,

FIG. 25 shows a partially cut view of the assembled drug deliverydevice,

FIG. 26 shows a longitudinal cross-section of the drive member beforereaching a zero dose configuration and

FIG. 27 is indicative of the drive member reaching the zero doseconfiguration.

DETAILED DESCRIPTION

As illustrated in FIGS. 1 and 2 the drug delivery device 10 comprises arather rectangular or cubic-shaped housing 20 comprising an upperhousing portion 21 and a lower housing portion 22. In the presentembodiment, the upper housing portion 21 may serve as a mounting base toassemble the components of the drive mechanism 3 thereon. The lowerhousing portion 22 may then serve as a cover, which preferablystabilises and keeps the various components of the drive mechanism 3 attheir positions. However, the roles of upper and lower housing portionsmay also be interchanged in alternative embodiments.

The rectangular shape of the housing 20 is particularly adapted to takeand to clasp the device 10 by one hand of a user. The drug deliverydevice 10 therefore comprises an elongated shape extending in axialdirection. In the present context, the axial distal direction is denotedwith reference number 1 and the opposite proximal direction is denotedwith reference number 2. The housing 20, in particular both of itshalves 21, 22, comprises a cartridge window 23.

The cartridge window 23 may comprise a recess in the upper and/or lowerhousing portion 21, 22 and may be at least partially transparent toallow visual inspection of a filling level of a cartridge 12 assembledinside the housing. The distal end of the housing 20 is further providedand protected by a removable cap 24. The cap 24 may positively engagewith a distal end of upper and lower housing portions 21, 22 in order toprotect a threaded socket 25 formed by upper and lower housing portions21, 22.

The threaded socket 25 is adapted to receive a needle assembly 15, inparticular a cup-shaped needle hub 16 providing a double-tippedinjection needle. In the various Figures, in particular in FIGS. 1, 2and in FIGS. 6 and 7, the needle assembly 15 is illustrated with aneedle cap 17, which is to be removed from the needle assembly 15 priorto conducting a dose dispensing procedure. The cartridge 12 to be fixedin the housing 20 comprises a tubular-shaped barrel filled with amedicament to be dispensed by the drug delivery device 10.

The barrel is sealed in proximal direction 2 by means of a piston 14,which is slidably disposed in axial direction 1, 2 inside the barrel ofthe cartridge 12. The piston 14 of the cartridge 12 is operablyengageable with a piston rod 120. The piston rod 120 of the drivemechanism 3 is operable to apply distally-directed thrust or pressure tothe piston 14 in order to drive the same in distal direction 1. In thisway, a fluid pressure may build up inside the cartridge 12.

When the distal dispensing end of the cartridge 12 is connected with theneedle assembly 15 in such a way, that a proximally extending tippedportion of the needle penetrates a distally-located seal of thecartridge, e.g. a septum, a predefined amount of the medicament can beexpelled from the cartridge 12 via the needle assembly 15 and intobiological tissue.

As indicated in FIG. 1, the housing 20 comprises a compartment 29adapted to receive the protective cap 24. For this purpose, the distalend face of the housing 20 comprises a slit 29 a as indicated in FIG. 5allowing to slidably receive the protective cap therein. Here, the slit29 a may serve as a hinge to pivot and to slidably receive the cap 24when the device is in use. In this way, the cap 24 is non-removablyattached to the housing 20 and cannot get lost.

In the following, setting of a dose is described.

For setting of a dose, the user typically takes or clasps the housing 20in one hand and starts to rotate, in particular to dial a dose settingmember 50 located in the upper housing portion 21. The dose settingmember 50 as illustrated in detail in FIG. 10 comprises acircular-shaped button comprising an outer rim and a central grippingbar 52 extending across the disc-shaped dose setting member 50. Thegripping bar 52 divides the dose setting member 50 into two recessesallowing for an intuitive and easy gripping thereof.

As indicated by the arrows in FIG. 10, the dose setting member 50 can berotated either clockwise 5, e.g. in a dose incrementing way orcounter-clockwise, e.g. in a dose decrementing way for incrementing ordecrementing a dose to be dispensed by the drug delivery device 10. Thedose setting member 50 is directly coupled to a dose indicatingarrangement as illustrated in FIGS. 10 and 11. The dose setting member50 as illustrated in cross-section of FIG. 12 is rotatably coupled witha dose indicating wheel 54.

As indicated in FIG. 12, the dose indicating wheel 54 comprises anaxially extending shaft received in a correspondingly-shaped receptacleof the dose setting member 50. Even though not illustrated, the shaftand the receptacle are splined. Shaft and receptacle of the doseindicating wheel 54 and the dose setting member 50 comprise at least oneprotrusion engaged with a correspondingly-shaped groove.

As further illustrated in FIG. 12, the receptacle 51 of the dose settingmember 54, in particular its sidewall is positively engaged with aninwardly extending fixing rim of the housing 20, thereby fixing the dosesetting member 50 in axial direction relative to the housing 20 butallowing the dose setting member 50 to rotate in either directionrelative to the housing 20.

The dose indicating wheel 54 serves as a first dose indicating wheel andcomprises a series of dose indicating numbers at its outer circumferenceas illustrated in FIG. 10. Here, the dose setting member 50 and thefirst dose indicating wheel 54 are coaxially aligned. The doseindicating wheel 54 may feature an outer rim substantially enclosing theouter circumference of the dose setting member 50.

Due to the splined and direct engagement of the dose setting member 50and the first dose indicating wheel 54, a rotation of the dose settingmember 50 in either direction directly transfers to a respectiverotation of the first dose indicating wheel 54. As a consequence, arespective number printed on a side of the dose indicating wheel 54shows up in a dose indicating window 26 of the housing 20 as illustratedin FIG. 25.

The first dose indicating wheel 54 comprises a sprocket 55 to engagewith an outer geared rim 59 of a gear wheel 58. The gear wheel 58 asillustrated in FIG. 11 comprises a further sprocket or pinion 60 axiallyoffset from the geared rim 59 of the gear wheel 58. As will be explainedlater on, the sprocket 60 is engaged with a toothed rack portion 71 of adrive member 70.

On the side opposite to the sprocket 60 the gear wheel 58 comprises arim structure 61 featuring isolated and separated cogs 62. Said cogs 62are operable to engage with a geared rim 57 or sprocket of a second doseindicating wheel 56. As illustrated in FIGS. 10 and 11, the second doseindicating wheel 56 provides a second series of ten digit representingnumbers of 10, 20, 30 and so on. By means of the isolated andcircumferentially separated cogs 62, a stepwise incrementing rotation ofthe second dose indicating wheel 56 can be attained when the first doseindicating wheel 54 rotates.

In effect, by means of the two dose indicating wheels 54, 56 all numbersof for instance between 0 and 120 can be illustrated in the doseindicating window 26 of the housing 20. Implementation of the twointerleaved dose indicating wheels 54, 56 allows for a rather largescale display so that even persons suffering impaired vision are enabledto read the illustrated numbers.

The first and the second dose indicating wheels 54, 56 further comprisea crown wheel 53, 57 a engaging with clicking members 31, 30 provided onthe inside of the oppositely disposed housing portion 21. As illustratedin FIG. 12, an inwardly extending pin-shaped clicking member 31 engageswith a crown wheel 53 located on a side face of the first doseindicating wheel 54. Correspondingly also the second dose indicatingwheel 56 comprises a crown wheel 57 a to mate with acorrespondingly-shaped clicking member 30 of the housing 20.

Mutual engagement of the first and second dose indicating wheels 54, 56with respective clicking members 31, 30 provides an audible click soundwhen the dose setting member 50 is rotated either in dose incrementingdirection or in dose decrementing direction. In this way, an audiblefeedback can be provided to the user when dialling the dose settingmember 50 in either direction.

As illustrated for instance in FIGS. 7, 8, 19 and 20 thecentrally-located sprocket 60 of the gear wheel 58 meshes with a toothedand elongated rack portion 71 of a drive member 70. The drive member 70is axially displaceable relative to a rotatable member 80, in thefollowing denoted as a drive spindle 80 extending therethrough. Thedrive member 70 comprises a sleeve portion 72 to receive the drivespindle 80, which is axially fixed in the housing 20 by means of abearing 33 as for instance illustrated in FIGS. 13 and 20.

As illustrated in detail in FIG. 15, the toothed rack portion 71 isconnected with the sleeve portion 72 via an interconnecting bar 73. Thetoothed rack portion 71 therefore radially outwardly extends from thesleeve portion 72 of the drive member 70. The drive member 70 is axiallydisplaceable relative to the drive spindle 80 and relative to thehousing 20 against the action of a spring element 78.

As illustrated in FIG. 15, the spring element 78 helically winds aroundthe drive spindle 80. The spring element 78 is preferably designed as acompression spring and can be tensioned by an upward, henceproximally-directed displacement of the drive member 70 relative to thedrive spindle 80. As further illustrated in FIG. 15, the sleeve portion72 of the drive member 70 comprises a radially outwardly extending rim76 at its distal end, which serves as a distal stop for the springelement 78.

Furthermore, the rim 76 comprises a radially outwardly extendingprotrusion 77 by way of which the drive member 70 can be axially guidedrelative to the housing 20. Moreover, the protrusion 77 may act as anaxial stopper for the drive member 70. As shown in FIG. 13, the housing20 comprises a proximal stop 27 and a distal stop 28 that are operableto engage with the radially outwardly extending protrusion 77 of thedrive member 70. In this way, axial displacement of the drive member 70relative to the housing 20 can be delimited in distal direction 1 aswell as in proximal direction 2.

The drive member 70 is further threadedly engaged with the drive spindle80. As illustrated in FIG. 13, the flange portion or rim 76 of the drivemember 70 comprises an inner thread 79 engaging with an outer thread 81of the drive spindle 80. Due to this threaded engagement and due to theaxial fixing of the drive spindle 80 to the housing 20, a displacementof the drive member 70 in proximal direction 2 against the action of thespring element 78 comes along with a dose incrementing rotation 5 of thedrive spindle 80.

Proximally-directed displacement of the drive member 70 relative to thehousing 20 can be induced by a dose incrementing rotation of the dosesetting member 50 and accordingly by a respective rotation of the gearwheel 58 and its sprocket 60. The axial length of the toothed rackportion 71 typically corresponds to the maximum distance the drivemember 70 is allowed to be displaced in distal direction 1 according tothe distance of the two stops 27 and 28.

Additionally, as illustrated in FIGS. 4 and 15, there is provided aprotruding ridge portion 75 on the side face of the toothed rack portion71. Said ridge portion 75 can be guided in a guiding structure 38 of thehousing 20 forming an elongated groove supporting the drive member 70and guiding the drive member 70 in axial direction.

The toothed rack portion 71 comprises consecutive teeth 74 at itslateral side portion to engage with the sprocket 60 of the gear wheel58.

Drive member 70 and drive spindle 80 form a kind of a spindle gear.Proximally-directed displacement of the drive member 70 comes along witha tensioning of the spring element 78 thereby rotating the drive spindle80 in a dose incrementing direction 5. The drive spindle 80 comprises atoothed rim 82 at its proximal end. As illustrated in cross-section ofFIG. 9, said toothed rim 82 engages with a radially outwardly extendinglatch element 153 of a ratchet member 150. The cup-shaped ratchet member150 acting as a clutch member 150 receives the toothed rim 82 of thedrive spindle 80 and inhibits a counter-directed, hence, a dosedecrementing rotation 6 of the drive spindle 80. Moreover, the latchelement 153 generally serves as a clutch element 153.

For this purpose, the latch element 153 comprises an arc-shape and atleast partially extends along the outer circumference of the toothed rim82 of the drive spindle 80. The latch element 153 serves as a clutchelement and the ratchet member 150 serves as a clutch member toselectively inhibit a rotation of the drive spindle 80. Typically,during dose setting, the latch or clutch element 153 meshes with aradially inwardly extending lug 154 with the teeth 83 of the toothed rim82.

The latch element 153 is either pivotal in radial direction (r) and/oris resiliently deformable in radial direction to engage with the teeth83 of the toothed rim 82 of the drive spindle 80. Depending on the slopeand geometry of mutually engaging teeth 83 and the lug 154, a doseincrementing rotation 5 as well as a dose decrementing rotation 6 of thedrive spindle 80 requires application of a respective actuation forceabove a predefined level or threshold.

The mutual engagement of the latch element 153 with the toothed rim 82is in any case sufficient to counterbalance the relaxing force of abiased spring element 78. In this way, the ratchet member 150 isoperable to keep the drive spindle 80 fixed, independent of the axialposition of the drive member 70 and the degree of tension of the springelement 78.

The spring element 78 may abut with its proximal end at the radiallyoutwardly extending toothed rim 82 of the drive spindle 80. In this way,the spring element 78 is axially constrained between the drive spindle80 and the drive member 70.

The distal end of the drive spindle 80 is provided with a pinion 86featuring a bearing portion 89 in form of a circumferential groove orrecess. As illustrated in FIGS. 13 and 20, the pinion 86 is supported bya bearing 33 of the housing 20, thereby axially and radially fixing thedrive spindle 80 in the housing 20. The pinion 86 comprises various cogsor teeth 88 engaging with a geared rim 93 of a drive sleeve 90. Thedrive sleeve 90 as illustrated in detail in FIGS. 14 and 15 comprises atubular-shaped sleeve portion and a radially extending flange portion 92at its distal end.

The flange portion 92 is provided with a geared rim 93 that meshes withthe pinion 86 of the drive spindle 80. Here, drive spindle 80 and drivesleeve 90 are permanently geared. Therefore, a dose incrementing as wellas a dose decrementing rotation of the drive spindle 80 always leads toa corresponding rotation of the drive sleeve 90.

Furthermore, the drive sleeve 90 at least partially encloses the pistonrod 120. The drive sleeve 90 is operably releasable from the piston rod120 during dose setting but is operably engageable with the piston rod120 for dispensing of a dose, as will be explained later on.

Radially sandwiched between the drive sleeve 90 and the piston rod 120there is provided a dose limiting member 130. The dose limiting member130 as illustrated in

FIG. 14 comprises a sleeve portion 132 featuring an outer thread 133engaged with an inner thread 95 of the drive sleeve 90. Moreover, thedose limiting member 130 comprises a proximally extending bracketportion 137 featuring two axially extending and parallely-orientedbranches 138, 139 that are mutually interconnected with their proximalends to form a closed frame structure.

As illustrated for instance in FIG. 15, a proximal end of the bracketportion 137 extends in proximal direction from a proximal end of thedrive sleeve 90. By means of the bracket portion 137, the dose limitingmember 130 can be rotatably fixed to the housing 20.

For instance, a correspondingly extending pin may protrude through theclosed frame structure of the bracket portion 137 in radial direction,thereby effectively inhibiting that the dose limiting member 130 rotatesas the drive sleeve 90 is set in rotation by means of the drive spindle80. Due to the threaded engagement of the dose limiting member 130 andthe drive sleeve 90 the dose limiting member 130 experiences aproximally-directed displacement relative to the drive sleeve 90 whenthe drive sleeve 90 is rotated in a dose incrementing direction 5.

Since a direct mechanical interaction or contact between the drivesleeve 90 and the piston rod 120 is not required, the dose limitingmember 130 can be arranged inside the drive sleeve 90 in a rathercontactless configuration relative to the piston rod 120, which alsoextends therethrough. Internal friction of the drive mechanism 3 cantherefore be reduced.

Moreover and as illustrated in FIG. 14, the piston rod 120 comprises astop member 124 which is adapted to engage with the dose limiting member130 when a maximum number of doses has been dispensed by the drivemechanism 3. In the present embodiment, the stop member 124 of thepiston rod 120 comprises a radially outwardly extending flange portionto engage with the proximally-located rim 136 of the sleeve portion 132of the dose limiting member 130. Preferably, the faces of the stopmember 124 and the sleeve portion 132 that face towards each other andwhich get in direct mutual contact when a last dose configuration isreached comprise a geared structure.

Hence, a distally-facing portion of the stop member 124 may comprise ageared flange, e.g. in form of a crown wheel 128. Correspondingly, alsothe proximal face of the sleeve portion 132 may comprise a geared rim ora crown wheel portion 136 to mate with the crown wheel 128 of the pistonrod 120. Such a configuration may be beneficial with such embodiments,where the piston rod 120 rotates when it is driven in distal direction 1during dose dispensing.

Mutually engaging crown wheels 128, 136 of the piston rod 120 and thedose limiting member 130 may then immediately inhibit any furtherrotation of the piston rod 120 relative to the rotatably fixed doselimiting member 130. Said mutual engagement is of particular benefit,when the complete content of the cartridge 12 has been expelled. Then,dose limiting member 130 and piston rod 120 are securely interlocked andeffectively impede any further incrementing dose setting.

The dose limiting member 130 effectively serves as a last dose limiter.In an initial configuration of the drive mechanism 3 as for instanceillustrated in FIG. 15, the dose limiting member 130 will travel inproximal direction 2 during a dose incrementing rotation of drivespindle 80 and drive sleeve 90. Since the dose setting of a single doseis limited by the axially confined displacement of the drive member 70,the dose limiting member 130 will at maximum reach a proximal endposition, in which the sleeve portion 132 still remains in the drivesleeve 90.

In such a configuration the dose limiting member 130 will be separatedfrom the stop member 124 of the piston rod 120. During a consecutivedose dispensing action, the piston rod 120 will advance in distaldirection 1 relative to the drive sleeve 90. Since a distally-directeddispensing displacement of the piston rod 120 comes along with a dosedecrementing rotation of the drive sleeve 90, also the dose limitingmember 130 will return into its initial zero dose configuration as forinstance illustrated in FIG. 14.

There may be provided a stop member inside the drive sleeve 90 toprovide a well-defined distal stop for the dose limiting member 130.However, such a zero dose stop is not necessarily required for the doselimiting member 130 since the dose decrementing rotation 6 of the drivesleeve 90 is already delimited by the drive member 70 engaging with adistal stop 28 of the housing 20.

With a consecutive dose setting procedure, the dose limiting member 130will repeatedly displace in axial direction 2. Since the piston rod 120has moved in distal direction 1 during the previous dose dispensingprocedure, the stop member 124 of the piston rod 120 continuouslyapproaches to the axial range in which the dose limiting member 130 isdisplaceable. If the position of the piston rod 120 corresponds to adose size smaller than the maximum size of a single dose, e.g. smallerthan 120 I.U., the stop member 124 of the piston rod 120 may enter thedrive sleeve 90 as for instance illustrated in FIG. 14.

In a proceeding dose setting procedure, the dose incrementing rotationof the drive sleeve 90 is immediately stopped, when theproximally-advancing dose limiting member 130 axially engages with thestop member 124 of the piston rod 120. In this way, it can be assured,that the sum of consecutive doses set and dispensed does not exceed thetotal amount of doses of the medicament contained in the cartridge 12.

The stop member 124 may comprise a lateral recess in order to receiveand to pass by the bracket portion 137 of the dose limiting member 130.Additionally or alternatively, it is also conceivable, that the doselimiting member 130 is splined to the piston rod 120 itself. As forinstance illustrated in FIG. 4, the dose limiting member 130 maycomprise a radially inwardly extending protrusion 135 to engage with anaxially extending groove 122 of the piston rod 120. In this way, thedose limiting member 130 can be rotatably locked to the piston rod 120.In such an alternative embodiment, the piston rod 120 should berotatably fixed to the housing. Here, the piston rod 120 could besplined to the housing 20.

In the following dispensing of a dose will be described.

For dispensing of a dose the drive sleeve 90 rotates in a dosedecrementing direction 6 in such a way, that the torque of the drivesleeve 90 is transferred to a distally-directed displacement of thepiston rod 120. As illustrated in FIG. 14, the drive sleeve 90 iscoaxially aligned with a drive nut or drive wheel 100. The drive wheel100 comprises a radially outwardly extending geared rim 102. The teethof said rim 102 comprise a saw tooth profile and engage with a ratchetmember 32 of the housing 20 as illustrated in FIG. 16.

By means of the mutual engagement of the ratchet member 32 with thegeared rim 102 rotation of the drive wheel 100 is only allowed in a dosedispensing or dose decrementing direction. A counter-directed movementis effectively blocked and inhibited by said engagement. Moreover,during a dose decrementing or dose dispensing rotation of the drivewheel 100, the ratchet member 32 generates an audible click soundthereby providing an audible feedback to the user, that the injection ordose dispensing is in progress.

The drive wheel 100 further comprises a through opening to receive thepiston rod 120 therethrough. The piston rod comprises an outer thread121 and/or a longitudinally extending groove 122. By means of a groove122 the piston rod 120 could be rotatably fixed to the housing 20. Bymeans of a threaded engagement of the piston rod 120 with an innerthread 104 of the drive wheel 100, the rotation of the axially fixeddrive wheel 100 can be transferred into a distally-directed displacementof the piston rod 120.

In an alternative but not illustrated embodiment, it is alsoconceivable, that the piston rod 120 is splined to the drive wheel 100and that the piston rod 120 is threadedly engaged with a housingportion. In such a technically equivalent configuration, rotation of thedrive wheel 100 equally transfers into a distally-directed displacementof the piston rod 120 relative to the housing 20 and relative to thebarrel of the cartridge 12.

A torque to rotate the drive wheel 100 is provided by the drive sleeve90, which is axially displaceable between a proximal stop position, inwhich the drive sleeve 90 is decoupled or disengaged from the drivewheel 100 and hence from the piston rod 120. In its distal stopposition, the drive sleeve 90 operably engages with the drive wheel 100in a torque transmissive way.

As for instance illustrated in FIG. 15, the drive sleeve 90 comprises aradially outwardly extending flange portion 92 at its distal end. Fromsaid flange portion 92, there extends a geared rim 93 radiallyoutwardly. The distal end face of the geared rim comprises a ringstructure to mate with a correspondingly-shaped flange portion of drivewheel's geared rim 102. Between the rim 102 and the rim 93 there isprovided a disc spring 110 which serves to displace the drive sleeve 90in proximal direction 2.

Hence, drive sleeve 90 and drive wheel 100 can be axially coupledagainst the action of the disc spring 110 positioned there between. Therim portions 93, 102 of drive sleeve 90 and drive wheel 100 carrying andsupporting the disc spring 110 are substantially flat-shaped. In orderto transfer angular momentum between the drive sleeve 90 and the drivewheel 100 the drive sleeve 90 comprises a crown wheel portion 94radially inwardly from the geared rim 93. Correspondingly, the drivewheel 100 comprises a proximally extending socket featuring acorrespondingly-shaped crown wheel 106.

When the drive sleeve 90 is displaced in distal direction 1 to get indirect contact with the drive wheel 100, said crown wheels 94, 106mutually engage and angular momentum acting on the drive sleeve 90 mayequally transfer to the drive wheel 100, thereby leading to adistally-directed displacement of the piston rod 120. Adistally-directed displacement of the drive sleeve 90 against the actionof the disc spring 110 is inducible by a dose dispensing button 40provided at a proximal end of the housing 20.

As for instance illustrated in FIG. 17, the dose dispensing button 40comprises a distally extending strut 41 to but against a proximal-facingportion of the radially outwardly extending flange portion 92 of thedrive sleeve 90. The strut 41 comprises a proximal rather axiallyextending strut portion 41 a and a distal strut portion 41 b whichextends at a predefined angle with respect to the axial direction. Inthis way, the strut 41 is at least resiliently deformable to a certaindegree so that a clutch between the drive sleeve 90 and the drive wheel100 remains engaged even when the position of the dose dispensing button40 in axial direction varies to a certain extent.

Depression of the dose dispensing button 40 in distal direction 1 notonly engages the drive sleeve 90 and the drive wheel 100. Additionally,distally-directed displacement of the dose dispensing button 40 leads toa release of the drive spindle 80 relative to the ratchet member 150.

As becomes apparent from a comparison of FIGS. 21 and 23, the latchelement 153 is resiliently deformable in radial direction. As shown inthe released configuration according to FIG. 23, the latch element 153radially protrudes from the outer circumference of the sidewall 156 ofthe cup-shaped ratchet member 150. In this configuration, the radiallyinwardly extending lug 154 provided at the free end of the resilientlydeformable latch element 153 is no longer engaged with the teeth 83 ofthe toothed rim 82 of the drive spindle 80.

In the released configuration the drive spindle 80 is effectively freeto rotate under the action of the relaxing spring element 78 and thespindle gear of drive spindle 80 and drive member 70 which is driven bysaid spring element 78.

In the locked or engaged configuration according to FIG. 21, thearc-shaped latch element 153 is biased radially inwardly so that itsradially inwardly extending lug 154 engages with the teeth 83 of thedrive spindle 80. Radially-directed displacement of the latch element153 is governed by a biasing member 144 provided at a proximal end of asleeve-shaped regulating member 140.

The regulating member 140 is rotatably and coaxially arranged to theratchet member 150 as for instance illustrated in FIGS. 22 and 24. Theregulating member 140 comprises a sleeve portion 141 featuring at leastone inclined slit 142 or a respective groove on its outer circumference.As illustrated in FIG. 21 the dose dispensing button 40 comprises aninwardly extending guiding member 42 featuring a radially inwardlyextending pin 43 engaging with the inclined slit 142 of the regulatingmember 140.

Due to the inclined orientation of the slit 142 relative to the axialdirection, a distally-directed displacement of the dose dispensingbutton 40 leads to continuous rotation of the regulating member 140. Asa consequence, the biasing member 144 travels along the outercircumference of the arc-shaped latch element 153. Here, the biasingmember 144 comprises a radially inwardly extending bulged portion 146which abuts with an outer circumference of the arc-shaped latch element153.

In the interlocked configuration, which corresponds to the dosedispensing button 40 in its proximal stop position, the biasing member144 is fairly close to the free end of the arc-shaped latch element 153.A depression of the dose dispensing button 40 in distal direction 1comes along with a corresponding rotation of the regulating member 140and leads to a continuous displacement of the biasing member 144 alongthe outer circumference of the arc-shaped latch element 153.

As a consequence and as illustrated in FIG. 23, the free end of thelatch element 153 may extend radially outwardly. Due to the engagementof the guiding member 42 of the dose dispensing button 40 with theinclined slit 142 of the regulating member 140, the degree of rotationof the regulating member 140 and its biasing member 144 is directlycorrelated to the degree of axial depression of the dose dispensingbutton 40.

Due to the resiliently deformable properties of the arc-shaped latchelement 153, the holding force provided by the latch element 153 andacting on the toothed rim 82 of the drive spindle 80 can be continuouslyand steplessly reduced or modified. In this way, mutual friction andgliding behaviour of the latch element 153 and the toothed rim 82 of thedrive spindle 80 can be modified in dependence of the depth or degree ofaxial depression of the dose dispensing button 40.

Depending on the degree of rotation of the regulating member 140, theholding force acting on the drive spindle 80 during an injectionprocedure can be continuously modified, thereby allowing to regulate theangular velocity of the drive spindle 80 when rotating in a dosedecrementing, hence in a dose dispensing orientation 6.

It is to be mentioned here, that the dispensing velocity regulationprovided by the mutual interaction of drive spindle 80 and ratchetmember 150 can be realized in a variety of different ways. Theorientation of the drive spindle 80 serving as a rotatable member and/orthe concrete mechanical interaction between the drive spindle 80 and theratchet member 150 may vary from the illustrated embodiment.

It is only required that the ratchet member 153, generally serving as aclutch member 153, is at least partially radially displaceable withrespect to the orientation of the axis of rotation 4 of the drivespindle 80 or of a respective rotatable element 80. Moreover, the mutualretarding interaction of ratchet member 150 and drive spindle 80 can befrictionally based. Additionally, a positive engagement of ratchetmember 150 and drive spindle 80 may also exhibit a combinedfriction-based and positively engaging interaction.

As further illustrated by a comparison of FIGS. 22 and 24, the dosedispensing button 40 is coupled with the proximal end of the ratchetmember 150 by means of a spring element 45, e.g. an injection spring 45,typically designed as a compression spring. As further illustrated inFIG. 21 the dose dispensing button 40 is intersected by a strut 44having a half shell shape which at least partially adopts the outercircumference of the ratchet member 150. In the half shell-shapedportion the strut 44 further comprises an additional pin 46 to engagewith a further slit 142 of the regulating member 140.

The regulating member 140 may therefore comprise two oppositely disposedslits 142 to engage with correspondingly arranged radially inwardlyextending pins 43, 46 of the dose dispensing button 40. The inwardlyextending guiding member 42 of the dose dispensing button 40 furthercomprises an outer guiding portion 42 a, which also adopts the outershape of the ratchet member 150. By means of the outer guiding portion42 a and the half shell strut 44, the dose dispensing button 40 can beaxially guided along the ratchet member 150.

For a secure fastening of the spring element 45, the proximal end of theratchet member 150 comprises a stepped portion 151 to receive the springelement 45 therein.

As becomes further apparent from FIGS. 21 and 22, the ratchet member 150comprises axially extended notches 155 that allow to guide the radiallyinwardly extending pins 43, 46 of the dose dispensing button 40 past theratchet member 150 during final assembly of the drive mechanism 3.

Depression of the dose dispensing button 40 in distal direction 1 fordispensing of a dose may then be divided into two consecutive steps. Ina first step the dose dispensing button 40 is displaced in distaldirection by a distance so that the pins 43, 46 advance in distaldirection 1 into the slits 142 of the regulating member 140. During thisinitial displacement the axially extending strut 41 already serves tomutually engage the drive sleeve 90 and the drive wheel 100.

In this way, a torque transmissive coupling of the drive sleeve 90 withthe piston rod 120 can be attained even before the drive spindle 80 andhence the drive member 70 are released from the ratchet member 150. Itis only due to a further depression of the dose dispensing button 40 indistal direction 1, that the pins 43, 46 run along the slit or groove142 leading to a releasing rotation of the regulating member 140 and toa gradual and continuous release of the latch element 153. The torquetransmissive coupling of drive sleeve 90 and piston rod prior to arelease of the drive spindle 80 from the ratchet member can becontrolled and governed by the flexural behaviour and by the geometricdesign of the latch element 153. As already explained above, the depthof depression of the dose dispensing button 40 may determine or may atleast influence the angular velocity of the drive spindle 80 during dosedispensing.

Under the action of the relaxing spring element 78, the drive member 70will return into its initial zero dose configuration. Since the toothedrack portion 71 of the drive member 70 is geared with the sprocket 60 ofthe gear wheel 58, the dose indicating wheel 54, 56 will count downaccordingly. Just before approaching an initial zero dose configuration,the drive member 70 may audibly engage with a clicking member 36 of thehousing 20.

As shown in FIG. 26, the drive member 70 comprises a ledge 75 a toengage with an inwardly extending pin-like clicking member 36. Justbefore reaching a zero dose configuration at the end of a dosedispensing procedure, the bevelled ledge 75 a engages with thecorrespondingly bevelled clicking member 36, thereby generating anaudible click sound, in particular when the resiliently deformableclicking member 36 returns into an initial abutment configuration withthe bevelled ledge 75 a as illustrated in FIG. 27. This audible feedbackindicates to the user that a dispensing procedure has terminated.

In the particular and illustrated embodiment, the rotatable member isembodied as a drive spindle 80, the clutch member is represented by aparticular ratchet member 150 and the clutch element is embodied as alatch element 153. In particular, every reference made in the followingto the drive spindle 80, to the ratchet member 150 and to the latchelement 153 correspondingly applies to the rotatable member, to theclutch member and to the clutch element, respectively.

LIST OF REFERENCE NUMERALS

-   1 distal direction-   2 proximal direction-   3 drive mechanism-   4 axis of rotation-   5 dose incrementing direction-   6 dose decrementing direction-   10 drug delivery device-   12 cartridge-   14 piston-   15 needle assembly-   16 needle hub-   17 needle cap-   20 housing-   21 upper housing portion-   22 lower housing portion-   23 cartridge window-   24 cap-   25 socket-   26 dose indicating window-   27 proximal stop-   28 distal stop-   29 receptacle-   29 a slit-   30 clicking member-   31 clicking member-   32 ratchet member-   33 bearing-   36 clicking member-   37 fixing rim-   38 guiding structure-   40 dose dispensing button-   41 strut-   41 a proximal strut portion-   41 b distal strut portion-   42 guiding member-   42 a outer guiding portion-   43 pin-   44 strut-   45 spring element-   46 pin-   50 dose setting member-   51 receptacle-   52 gripping bar-   53 crown wheel-   54 dose indicating wheel-   55 sprocket-   56 dose indicating wheel-   57 geared rim-   57 a crown wheel-   58 gear wheel-   59 geared rim-   60 sprocket-   61 ring structure-   62 cog-   70 drive member-   71 toothed rack portion-   72 sleeve portion-   73 bar-   74 tooth-   75 ridge portion-   75 a ledge-   76 rim-   77 protrusion-   78 spring element-   79 inner thread-   80 drive spindle-   81 outer thread-   82 toothed rim-   83 tooth-   86 pinion-   88 tooth-   89 bearing portion-   90 drive sleeve-   92 flange portion-   93 geared rim-   94 crown wheel-   95 inner thread-   100 drive wheel-   102 geared rim-   104 inner thread-   106 crown wheel-   110 disc spring-   120 piston rod-   121 thread-   122 groove-   124 stop member-   126 pressure piece-   128 crown wheel-   130 dose limiting member-   132 sleeve portion-   133 outer thread-   135 protrusion-   136 geared rim-   137 bracket portion-   138 branch-   139 branch-   140 regulating member-   141 sleeve portion-   142 slit-   144 biasing member-   146 bulged portion-   150 ratchet member-   151 stepped portion-   153 latch element-   154 lug-   155 notch-   156 sidewall

1. A drive mechanism of a drug delivery device for setting anddispensing of a dose of a medicament, the mechanism comprising: ahousing (20), a piston rod (120) to operably engage with a piston (14)of a cartridge (12) to displace the piston (14) in a distal direction(1), a rotatable member (80) arranged on an axially extending axis ofrotation (4) in the housing (20), said rotatable member (80) beingrotatable in a dose incrementing direction (5) against the action of aspring element (78) and being operably engageable with the piston rod(120) during dose dispensing, a clutch member (150) comprising at leastone radially displaceable clutch element (153) to engage with a rim (82)of the rotatable member (80) with variably adjustable strength.
 2. Thedrive mechanism according to claim 1, wherein the clutch element (153)is pivotally supported in radial direction.
 3. The drive mechanismaccording to any one of the preceding claims, wherein the clutch element(153) is resiliently deformable in radial direction (r).
 4. The drivemechanism according to any one of the preceding claims, wherein theclutch element (153) comprises an arc-shape and at least partiallyextends along the outer circumference of the outer rim (82) of therotatable member (80).
 5. The drive mechanism according to any one ofthe preceding claims, wherein the clutch element (153) comprises aradially inwardly extending lug (154) at a free end portion thereof toengage with the outer rim (82) of the rotatable member (80).
 6. Thedrive mechanism according to any one of the preceding claims, whereinthe clutch element (153) and the outer rim (82) of the rotatable member(80) are frictionally engageable.
 7. The drive mechanism according toany one of the preceding claims, wherein the clutch element (153) andthe rotatable member (80) are positively engageable.
 8. The drivemechanism according to any one of the preceding claims, furthercomprising a regulating member (140) at least radially enclosing theclutch element (153) and comprising a biasing member (144) to radiallyengage with the clutch element (153).
 9. The drive mechanism accordingto claim 8, wherein the regulating member (140) is rotatable relative tothe clutch element (153).
 10. The drive mechanism according to any oneof the preceding claim 8 or 9, wherein the regulating member (140)comprises an axially extending sleeve portion (141) having at least oneinclined groove or slit (142) engaged with at least one axiallydisplaceable pin (43, 46) of a dose dispensing member (40).
 11. Thedrive mechanism according to claim 10, wherein the dose dispensingmember (40) is slidably axially displaceable relative to the regulatingmember (140) against the action of a spring element (45).
 12. The drivemechanism according to any one of the preceding claim 10 or 11, whereinthe mutual engagement of dose dispensing member (40), regulating member(140), clutch member (150) and rotatable member (80) is such that anangular velocity of a spring element-induced rotation of the rotatablemember (80) in a dose dispensing direction (6) is adjustable by theaxial displacement of the dose dispensing member (40) relative to theregulating member (140).
 13. The drive mechanism according to any one ofthe preceding claims 10 to 12, wherein when the dose dispensing member(40) is located in a proximal stop position of the at least one grooveor slit (142) of the regulating member (140) substantially axiallyflushes with a radially inwardly extending notch (155) provided at theouter circumference of the clutch member (150).
 14. The drive mechanismaccording to any one of the preceding claims, wherein the rotatablemember (80) comprises a drive spindle (80) or a drive sleeve (90)rotatably engaged with a rotatable dose setting member (50) for rotatingthe dose setting member (50) in a dose incrementing direction (5) and/orin a dose decrementing direction (6) during dose setting and/or duringdose dispensing.
 15. A drug delivery device for setting and dispensingof a dose of a medicament, the device comprises: a drive mechanism (3)according to any one of the preceding claims, and a cartridge (12)containing the medicament and being arranged in the housing (20) of thedrive mechanism (3).